Heterogeneity in response to serological exposure markers of recent Plasmodium vivax infections in contrasting epidemiological contexts.
Heterogeneity in response to serological exposure markers of recent Plasmodium vivax infections in contrasting epidemiological contexts.
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在对比流行病学背景下，对近期间日疟原虫感染血清学暴露标志物的异源性应答
DOI：
10.1371/journal.pntd.0009165
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发表时间：
2021-03
影响因子：
3.8
通讯作者：
Mueller I
中科院分区：
文献类型：
--
作者：
Rosado J;White MT;Longley RJ;Lacerda M;Monteiro W;Brewster J;Sattabongkot J;Guzman-Guzman M;Llanos-Cuentas A;Vinetz JM;Gamboa D;Mueller I
抗体反应作为间日疟原虫感染的血清学标记物已被证明与暴露相关，但对影响流行环境中自然感染者抗体反应的其他因素所知甚少。为了解决这个问题，我们研究了在三种不同传播强度的环境中，IgG对间日疟原虫新型血清学暴露标志物（SEMs）的反应。我们使用多重平台对秘鲁队列中的34个SEMs进行了长达三年的纵向随访，并将结果与泰国和巴西队列的数据进行了比较。使用线性回归模型来表征抗体反应与年龄、随访期间检测到的血期感染数量以及自上次感染以来的时间之间的关系。采用受试者工作特征（Receiver Operating Characteristic， ROC）分析，检验sem对前9个月间日疟原虫感染的识别能力。抗体滴度与所有三个研究地点的年龄、血期感染次数和之前感染间日疟原虫的时间有关。在泰国和巴西的低传播环境中，与秘鲁的高传播环境相比，抗体滴度与上次间日疟原虫感染后的时间之间的相关性更强。在测试的SEMs中，RBP2b抗体反应在所有地点对近期暴露进行分类的性能最高，泰国的ROC曲线下面积(AUC) = 0.83，巴西的AUC = 0.79，秘鲁的AUC = 0.68。在低传播环境中，间日疟原虫sem可以准确识别近期血期感染的个体。在更高的传输设置中，这种方法的准确性大大降低。我们建议在追求消除疟疾的低传播环境中使用间日疟原虫sme，但它们在注重疟疾控制的高传播环境中可能效果较差。间日疟原虫由于能够引起反复感染，在许多国家仍然构成威胁。实现消除疟疾目标的关键是能够迅速发现和治疗复发寄生虫携带者。如果不能确定这一传播宿主，将阻碍消除疟疾的进展。最近，在低传播环境中开发并验证了最近暴露于间日疟原虫（SEM）的新型血清学标记物。当在不同的地方病环境中进行评估时，人们对影响抗体对这些标记物反应的因素仍然知之甚少。为了确定影响抗体对SEM反应的因素，我们比较了三个不同传播强度地点的抗体水平：泰国（低）、巴西（中等）和秘鲁（高）。在这项研究中，我们发现传播强度在间日疟原虫抗体库的获得中起着关键作用。在高流行地区，由于持续和持续暴露而产生的免疫记忆可能会影响sem检测最近暴露于间日疟原虫的个体的性能。总之，在低传输站点表现良好的sem在高传输区域表现不佳。
Antibody responses as serological markers of Plasmodium vivax infection have been shown to correlate with exposure, but little is known about the other factors that affect antibody responses in naturally infected people from endemic settings. To address this question, we studied IgG responses to novel serological exposure markers (SEMs) of P. vivax in three settings with different transmission intensity. We validated a panel of 34 SEMs in a Peruvian cohort with up to three years’ longitudinal follow-up using a multiplex platform and compared results to data from cohorts in Thailand and Brazil. Linear regression models were used to characterize the association between antibody responses and age, the number of detected blood-stage infections during follow-up, and time since previous infection. Receiver Operating Characteristic (ROC) analysis was used to test the performance of SEMs to identify P. vivax infections in the previous 9 months. Antibody titers were associated with age, the number of blood-stage infections, and time since previous P. vivax infection in all three study sites. The association between antibody titers and time since previous P. vivax infection was stronger in the low transmission settings of Thailand and Brazil compared to the higher transmission setting in Peru. Of the SEMs tested, antibody responses to RBP2b had the highest performance for classifying recent exposure in all sites, with area under the ROC curve (AUC) = 0.83 in Thailand, AUC = 0.79 in Brazil, and AUC = 0.68 in Peru. In low transmission settings, P. vivax SEMs can accurately identify individuals with recent blood-stage infections. In higher transmission settings, the accuracy of this approach diminishes substantially. We recommend using P. vivax SEMs in low transmission settings pursuing malaria elimination, but they are likely to be less effective in high transmission settings focused on malaria control. Plasmodium vivax still poses a threat in many countries due to its ability to cause recurrent infections. Key to achieving the goal of malaria elimination is the ability to quickly detect and treat carriers of relapsing parasites. Failing to identify this transmission reservoir will hinder progress towards malaria elimination. Recently, novel serological markers of recent exposure to P. vivax (SEM) have been developed and validated in low transmission settings. It is still poorly understood what factors affect the antibody response to these markers when evaluated in contrasting endemic contexts. To determine the factors that influence the antibody response to SEM, we compared the antibody levels in three sites with different transmission intensity: Thailand (low), Brazil (moderate) and Peru (high). In this study, we found that transmission intensity plays a key role in the acquisition of the antibody repertoire to P. vivax. In highly endemic sites, it is likely that immunological memory resulting from a constant and sustained exposure will impact the performance of SEMs to detect individuals with recent exposure to P. vivax. In summary, SEMs that perform well in low transmission sites do not perform as well in high transmission regions.
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影响因子：
3.8
作者：
He, Wen-Qiang;Shakri, Ahmad Rushdi;Mueller, Ivo
通讯作者：
Mueller, Ivo
影响因子：
3
作者：
Fernandez-Becerra C;Sanz S;Brucet M;Stanisic DI;Alves FP;Camargo EP;Alonso PL;Mueller I;del Portillo HA
通讯作者：
del Portillo HA
DOI：
10.1073/pnas.0408725102
发表时间：
2005-04-05
影响因子：
11.1
作者：
Drakeley, CJ;Corran, PH;Riley, EM
通讯作者：
Riley, EM
影响因子：
3
作者：
Kochayoo，Piyawan;Changrob，Siriruk;Han，Eun-Taek
通讯作者：
Han，Eun-Taek
影响因子：
7.7
作者：
França CT;White MT;He WQ;Hostetler JB;Brewster J;Frato G;Malhotra I;Gruszczyk J;Huon C;Lin E;Kiniboro B;Yadava A;Siba P;Galinski MR;Healer J;Chitnis C;Cowman AF;Takashima E;Tsuboi T;Tham WH;Fairhurst RM;Rayner JC;King CL;Mueller I
通讯作者：
Mueller I